LDLR and Hypocholesterolemia: R46L is also a LOF PCSK9 mutation, the R46L-PCSK9 undergoes near normal autocatalytic cleavage and is secreted, yet cells expressing the mutant displayed a 16% increase in of cell surface LDLR and a 35% increase in internalized LDL compared with WT-PCSK9, suggesting that R46L causes hypocholesterolemia through a decreased ability to degrade LDLR (Cameron et al., 2006).